Left ventricular reverse remodelling as a promising strategy for resolving left ventricular thrombus.

AIMS: Recent years, several studies have suggested that abnormal baseline left ventricular (LV) function and structure are associated with left ventricular thrombus (LVT) formation. Despite this, most studies have given less attention to the potential role of left ventricular reverse remodelling (LVRR), that is, the improvement of LV function and structure, in resolving LVT. In this study, we aim to investigate the clinical characteristics, prognosis, and LVT resolution in patients with LVRR. METHODS AND RESULTS: This is a retrospective study conducted at The First Affiliated Hospital of Dalian Medical University. Our cohort consists of patients diagnosed with LVT between 1 November 2015 and 31 May 2020. Enrolled patients were categorized into two groups: LVRR and Failure of LVRR. The primary endpoints included LVT resolution and embolic events. A total of 84 patients were included in the study, with 59 patients in the LVRR group and 25 patients in the Failure of LVRR group. In our study, patients in the LVRR group experienced higher incidence of LVT resolution and a lower risk of embolic events. Multivariate logistic analysis revealed that Failure of LVRR was the only independent negative predictor for LVT resolution and positive predictor for embolic events. CONCLUSIONS: Patients with LVRR experience higher incidence of LVT resolution and have lower risk of embolic events, highlighting the significance of identifying and mitigating risk factors that contribute to abnormal LV function and structure in management of patients with LVT.

Predictors and prognostic implications of left ventricular ejection fraction trajectory improvement in the spectrum of heart failure with reduced and mildly reduced ejection fraction.

BACKGROUND: The latest guidelines emphasize the significance of evaluating the left ventricular ejection fraction (LVEF) trajectory in patients with heart failure (HF). Because patients with HF with reduced ejection fraction (HFrEF) and HF with mildly reduced ejection fraction (HFmrEF) have reduction in systolic function, they might be in a trajectory of LVEF improvement after medical and device-based therapies. While previous studies have primarily focused on LVEF improvement in HFrEF, there is limited research on LVEF trajectory improvement across the spectrum of HFrEF and HFmrEF. This study aimed to assess the determinants and prognostic implications of LVEF trajectory improvement in HFrEF and HFmrEF patients. METHODS: The cohort was classified into the improved group (HFrEF-to-HF with improved ejection fraction (HFimpEF) and HFmrEF-to-HF with preserved ejection fraction (HFpEF)) and the unimproved group (lack of improved group criteria). The primary endpoints were the composite of all-cause mortality or HF hospitalization, all-cause mortality, and HF hospitalization. Predictors of LVEF trajectory improvement were also evaluated. RESULTS: A total 1303 patients were included in the study (improved/unimproved group: n = 497/806). Cox regression analysis showed that the improved group experienced lower risks of prespecified end points than the unimproved group. Multivariate logistic regression analysis showed that atrial flutter, use of spironolactone, and treatment with catheter ablation were associated with LVEF trajectory improvement, while myocardial infarction, prior percutaneous catheter intervention or coronary artery bypass graft, E/e', and left ventricular end-diastolic diameter were identified as negative predictors of LVEF trajectory improvement. In the improved subgroup, the prognosis for the HFrEF-to-HFimpEF and HFmrEF-to-HFpEF was comparable. CONCLUSIONS: LVEF trajectory improvement patients had improved clinical outcomes and it was associated with important clinical, baseline cardiac structure and function, and treatment factors. Outcomes were similar in both HFrEF-to-HFimpEF and HFmrEF-to-HFpEF subgroups. These results suggest that emphasis should be placed on LVEF trajectory improvement to improve the outcomes of this population.

Trajectory change of left ventricular ejection fraction after rhythm control for atrial fibrillation in heart failure.

AIMS: Rhythm control therapy has shown great benefits for patients with atrial fibrillation (AF) and heart failure (HF). However, few studies have evaluated the effects of rhythm control on left ventricular ejection fraction (LVEF) trajectory across the whole HF spectrum. Our study explored the prevalence and predictors of LVEF trajectory changes and their prognostic implications following rhythm control. METHODS AND RESULTS: Depending on the treatment strategy, the cohort was classified into rhythm and rate control groups. Alterations in HF types and LVEF trajectory were recorded. The observational endpoints were all-cause mortality and HF-related admission. Predictors of LVEF trajectory improvement in the rhythm control group were evaluated. After matching, the two groups had similar age [mean age (years): rhythm/rate control: 63.96/65.13] and gender [male: rhythm/rate control: n = 228 (55.6%)/233 (56.8%)]. Based on baseline LVEF measurement, the post-matched cohort had 490 HF with preserved ejection fraction (rhythm/rate control: n = 260/230; median LVEF: 58.00%/57.00%), 99 HF with mildly reduced ejection fraction (rhythm/rate control: n = 50/49; median LVEF: 45.00%/46.00%), and 231 HF with reduced ejection fraction (rhythm/rate control: n = 100/131; median LVEF: 32.50%/33.00%). Trajectory analysis found that the rhythm control group had a greater percentage of LVEF trajectory improvement than the rate control group [80 (53.3%) vs. 71 (39.4%), P = 0.012]. Cox regression analysis also showed that the rhythm control group was more likely to have improved LVEF trajectory compared with the rate control group {hazard ratio [HR] 1.671 [95% confidence interval (CI) 1.196-2.335], P = 0.003}. In the survival analysis, the rhythm control group experienced significant lower risks of all-cause mortality [HR 0.600 (95% CI 0.366-0.983), P = 0.043] and HF-related admission [HR 0.611 (95% CI 0.496-0.753), P < 0.001]. In the rhythm control subgroup, E/e' [odds ratio (OR) 0.878 (95% CI 0.792-0.974), P = 0.014], left ventricular end-diastolic diameter [OR 0.874 (95% CI 0.777-0.983), P = 0.024], and CHA2DS2-VASc score (congestive HF, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65-74 years, and sex category) [OR 0.647 (95% CI 0.438-0.955), P = 0.028] were identified as three independent predictors of LVEF trajectory improvement. CONCLUSIONS: Rhythm control is associated with improved LVEF trajectory and clinical outcomes and may thus be considered the optimal therapeutic strategy for patients with both HF and AF.

Effects of rhythm control on left atrial structure remodeling in atrial fibrillation and heart failure with preserved ejection fraction.

Background: The benefits of rhythm control for atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF) have not been conclusively determined. We assessed the effects of rhythm control on left atrial (LA) structure remodeling and prognosis in patients with AF and HFpEF. Methods: This was a retrospective, real-world, observational study involving patients diagnosed with AF and HFpEF. The cohort was divided into rhythm-control and rate-control groups depending on their treatment strategies. The primary outcomes were all-cause mortality, rehospitalization for any cause, HF-related rehospitalization, and stroke. Differences in follow-up LA structure parameters were also analyzed. Results: Compared to the rate-control group, patients in the rhythm-control group had a lower risk of HF-related rehospitalization even after adjusting for potential confounders (adjusted HR 0.605, 95% CI 0.413-0.887, p = 0.010). Moreover, rhythm-control therapy led to marked reductions in LA echocardiographic indicators and a higher proportion of LA reverse remodeling (LARR). Conclusions: Rhythm-control therapy reverses LA structure remodeling and is associated with improved clinical outcomes; therefore, it is an optimal treatment approach for AF in HFpEF patients.

Prognostic implications of left ventricular ejection fraction trajectory changes in heart failure.

Aims: The latest guidelines recommended to assess the trajectory of left ventricular ejection fraction (LVEF) in patients with heart failure (HF). However, there is limited data on the trajectory of LVEF in real-world settings. In this study, we investigated the frequency and prognostic implications of changes in LVEF trajectory. Methods: Patients were divided into intensified LVEF, static LVEF, and worsening LVEF groups based on the transitions of HF types from baseline to follow-up. The intensified and worsening LVEF groups were further subdivided into mild (≤10% absolute changes of LVEF) and significant (>10% absolute changes of LVEF) increase or decrease groups according to the magnitude of change. The incidences and associations of changes in LVEF with patient outcomes were analyzed. Results: Among the 2,429 patients in the study cohort, 38.3% of HF with reduced ejection fraction (HFrEF) and 37.6% of HF with mildly reduced ejection fraction (HFmrEF) showed an improvement in their LVEF. In contrast, a decline in LVEF was observed in 19.3% of HF patients with preserved ejection fraction (HFpEF) and 34.9% of those with HFmrEF. Cox regression analysis showed that the intensified LVEF group was associated with a lower risk of composite endpoints, while the worsening LVEF group yielded opposite findings. Subgroup analysis revealed that compared to those with mild changes in LVEF, baseline HFrEF patients with significant increase showed a lower risk of composite outcome, while baseline HFpEF patients were the opposite. Conclusions: The trajectories of LVEF changes are strongly correlated with outcomes in patients with HF who had prior history of HF admission. The most significant prognostic implications observed in patients with significant LVEF changes. Trajectory LVEF and type of HF changes are useful tools recommended for prognostication.

Effects of Rhythm Control for Atrial Fibrillation on Cardiac Remodeling and Valvular Regurgitation in Patients with Heart Failure.

PURPOSE: Previous studies investigating cardiac remodeling and functional regurgitation of rhythm control for atrial fibrillation (AF) in heart failure (HF) are limited. Therefore, this study aimed to evaluate the impact of rhythm control for AF on cardiac remodeling and functional regurgitation in the spectrum of HF. Its effect on prognosis was explored. METHODS: According to the treatment strategies of AF, the cohort was classified into the rhythm control and rate control groups. To further detect the implications of rhythm control on cardiac remodeling, functional regurgitation, and outcomes in HF subtypes, patients were further divided into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction, and HF with preserved ejection fraction (HFpEF) subgroups. RESULTS: A total of 828 patients were enrolled, with 307 patients in the rhythm control group and 521 patients in the rate control group. Over a median follow-up time of 3.8 years, patients with rhythm control treatments experienced improvements in biatrial structure parameters, left ventricular ejection fraction, and functional regurgitation (mitral and tricuspid regurgitation) compared with rate control treatment (p < 0.05). Cox regression analysis demonstrated that rhythm control reduced the risks of all-cause mortality (HR 0.436 [95% CI, 0.218-0.871], p = 0.019) in HFpEF and HF-related admissions in HFrEF (HR 0.500 [95% CI, 0.330-0.757], p = 0.001) and HFpEF (HR 0.541 [95% CI, 0.407-0.720], p < 0.001); these associations were similar after adjusting for multiple confounders. CONCLUSIONS: Rhythm control therapy can be considered an appropriate treatment strategy for the management of AF in HF to improve cardiac remodeling, functional regurgitation, and prognosis.

Private placements of equity and accessibility of bank loans.

This study investigates the changes in quantity and cost of bank loans after a private placement of common stocks by A-share listed companies in China from 2011 to 2021. This research is derived from the signaling theory and is based on a difference-in-difference design. Through propensity score matching, the sample comprises companies that placed equity privately in the experiment group and companies that did not place equity privately in the control group. We find evidence that the increase in bank loans slowed down, and the cost of bank loans increased after the private placement. The signaling effect of private placements is robust to various additional tests. Further analysis indicates that when state-owned enterprises place equity privately, their access to bank loans is not affected. When institutional investors participate in the private placement, the company's access to bank credit does not go through significant changes. In addition, private placements by companies located in regions with higher levels of marketization of the financial market do not reduce the cost of bank loans.

Reverse Atrial Remodeling in Heart Failure With Recovered Ejection Fraction.

Background Heart failure with recovered ejection fraction (HFrecEF) has been a newly recognized entity since 2020. However, the concept has primarily focused on left ventricular ejection fraction improvement, with less focus on the recovery of the left atrium. In this study, we investigated changes in left atrial (LA) echocardiographic indices in HFrecEF. Methods and Results An inpatient cohort with heart failure with reduced ejection fraction (HFrEF) was identified retrospectively and followed up prospectively in a single tertiary hospital. The enrolled patients were classified into HFrecEF and persistent HFrEF groups. Alternations in LA parameters by echocardiography were calculated. The primary outcome was a composite of cardiovascular death or heart failure rehospitalization. A total of 699 patients were included (HFrecEF: n=228; persistent HFrEF: n=471). Compared with persistent HFrEF, the HFrecEF group had greater reductions in LA diameter, LA transverse diameter, LA superior-inferior diameter, LA volume, and LA volume index but not in LA sphericity index. Cox regression analysis showed that the HFrecEF group experienced lower risks of prespecified end points than the persistent HFrEF group after adjusting for confounders. Additionally, 136 (59.6%) and 62 (13.0%) patients showed LA reverse remodeling (LARR) for the HFrecEF and persistent HFrEF groups, respectively. Among the HFrecEF subgroup, patients with LARR had better prognosis compared with those without LARR. Multivariate logistic analysis demonstrated that age and coronary heart disease were 2 independent negative predictors for LARR. Conclusions In HFrecEF, both left ventricular systolic function and LA structure remodeling were improved. Patients with HFrecEF with LARR had improved clinical outcomes, indicating that the evaluation of LA size provides a useful biomarker for risk stratification of heart failure.

Efficacy of guideline-directed medical treatment in heart failure with mildly reduced ejection fraction.

AIMS: Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline-directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, ß-blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. METHODS: This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple-drug therapy (TT) and non-triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. RESULTS: Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all-cause mortality (HR 0.656, 95% CI 0.447-0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380-0.946, P = 0.028), any-cause rehospitalization (HR 0.687, 95% CI 0.541-0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565-0.948, P = 0.018). CONCLUSIONS: In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF.

Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer.

Exosomal transfer of oncogenic miRNAs can enhance recipient cell growth, metastasis and chemoresistance. Currently we found that microRNA-501-5p (miR-501) was overexpressed in doxorubicin-resistant gastric cancer (GC) SGC7901/ADR cell-secreted exosomes (ADR Exo) than that in SGC7901 cell-secreted exosomes (7901 Exo). ADR Exo was internalized by SGC7901, and a Cy3-miR-501 mimic was transferred from SGC7901/ADR to SGC7901 via exosomes. ADR Exo conferred doxorubicin resistance, proliferation, migration and invasion abilities to negative control miRNA inhibitor-expressing GC cells, whereas it inhibited apoptosis. MiR-501 knockdown or BH3-like motif-containing protein, cell death inducer (BLID) overexpression could reverse the effects of ADR Exo on recipient cells. SGC7901 cells cocultured with SGC7901/ADR prior to treatment with GW4869 or transfection of a miR-501 inhibitor were sensitive to doxorubicin and exhibited attenuated proliferation, migration and invasion and increased apoptosis. The intratumoral injection of ADR Exo into negative control miRNA inhibitor-expressing SGC7901 cells induced rapid subcutaneous tumor growth and resistance to doxorubicin compared to that of miR-501 knockdown or BLID-overexpressing cells. This effect is possibly achieved by exosomal miR-501-induced downregulation of BLID, subsequent inactivation of caspase-9/-3 and phosphorylation of Akt. Exosomal miR-501 might be a therapeutic target for GC.

Dose-dependent pharmacokinetics of tyrosol galactoside as an anti-fatigue drug in rats.

Tyrosol galactoside (TG) is a new candidate anti-fatigue agent under development. In order to have a good understanding of its pharmacokinetic characters, the paper describes the dose-dependent pharmacokinetics of TG in rats after oral and intravenous administration. TG was rapidly absorbed after oral administration and cleared with first-order rate, for the plasma half-life was independent of dose. C(max) and AUC(0-infinity) after both intravenous and oral dosing were all linearly correlated with the dose, as the regression correlation coefficient (R) was 0.998, 0.989 and 0.994 for AUC(0-infinity) (i.v., P < 0.01) AUC(0-infinity) (i.g., P < 0.01) and C(max) (i. g., P < 0.01), respectively. However, these parameters increased less than proportionally with increasing dose. In addition, the apparent volume of distribution (Vd) and the apparent clearance (Cl) seemed to be affected by the dose.